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PLGA-壳聚糖包载 IL-10 纳米颗粒调控小鼠沙眼衣原体感染炎症反应

PLGA-Chitosan Encapsulated IL-10 Nanoparticles Modulate Chlamydia Inflammation in Mice.

机构信息

Center for NanoBiotechnology Research (CNBR), Alabama State University, Montgomery, AL, USA.

Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA.

出版信息

Int J Nanomedicine. 2024 Feb 8;19:1287-1301. doi: 10.2147/IJN.S432970. eCollection 2024.

Abstract

INTRODUCTION

Interleukin-10 (IL-10) is a key anti-inflammatory mediator in protecting host from over-exuberant responses to pathogens and play important roles in wound healing, autoimmunity, cancer, and homeostasis. However, its application as a therapeutic agent for biomedical applications has been limited due to its short biological half-life. Therefore, it is important to prolong the half-life of IL-10 to replace the current therapeutic application, which relies on administering large and repeated dosages. Therefore, not a cost-effective approach. Thus, studies that aim to address this type of challenges are always in need.

METHODS

Recombinant IL-10 was encapsulated in biodegradable nanoparticles (Poly-(Lactic-co-Glycolic Acid) and Chitosan)) by the double emulsion method and then characterized for size, surface charge, thermal stability, cytotoxicity, in vitro release, UV-visible spectroscopy, and Fourier Transform-Infrared Spectroscopy as well as evaluated for its anti-inflammatory effects. Bioactivity of encapsulated IL-10 was evaluated in vitro using J774A.1 macrophage cell-line and in vivo using BALB/c mice. Inflammatory cytokines (IL-6 and TNF-α) were quantified from culture supernatants using specific enzyme-linked immunosorbent assay (ELISA), and significance was analyzed using ANOVA.

RESULTS

We obtained a high 96% encapsulation efficiency with smooth encapsulated IL-10 nanoparticles of ~100-150 nm size and release from nanoparticles as measurable to 22 days. Our result demonstrated that encapsulated IL-10 was biocompatible and functional by reducing the inflammatory responses induced by LPS in macrophages. Of significance, we also proved the functionality of encapsulated IL-10 by its capacity to reduce inflammation in BALB/c mice as provoked by , an inflammatory sexually transmitted infectious bacterium.

DISCUSSION

Collectively, our results show the successful IL-10 encapsulation, slow release to prolong its biological half-life and reduce inflammatory cytokines IL-6 and TNF production in vitro and in mice. Our results serve as proof of concept to further explore the therapeutic prospective of encapsulated IL-10 for biomedical applications, including inflammatory diseases.

摘要

简介

白细胞介素-10(IL-10)是一种关键的抗炎介质,可保护宿主免受病原体过度反应的影响,并在伤口愈合、自身免疫、癌症和体内平衡中发挥重要作用。然而,由于其生物学半衰期短,其作为生物医学应用的治疗剂的应用受到限制。因此,延长 IL-10 的半衰期以替代当前依赖于大剂量和重复剂量的治疗应用非常重要。因此,这不是一种具有成本效益的方法。因此,总是需要研究旨在解决此类挑战的方法。

方法

通过复乳法将重组白细胞介素-10 包封在可生物降解的纳米颗粒(聚(乳酸-共-乙醇酸)和壳聚糖)中,然后对其大小、表面电荷、热稳定性、细胞毒性、体外释放、紫外可见光谱和傅里叶变换-红外光谱进行表征,并评估其抗炎作用。使用 J774A.1 巨噬细胞系在体外和 BALB/c 小鼠在体内评估包封的白细胞介素-10 的生物活性。使用特定的酶联免疫吸附测定(ELISA)从培养上清液中定量炎性细胞因子(IL-6 和 TNF-α),并使用 ANOVA 分析其显著性。

结果

我们获得了 96%的高包封效率,得到了~100-150nm 大小的光滑包封的白细胞介素-10 纳米颗粒,从纳米颗粒中的释放可测量到 22 天。我们的结果表明,包封的白细胞介素-10 通过减少 LPS 在巨噬细胞中诱导的炎症反应而具有生物相容性和功能。值得注意的是,我们还通过其降低由炎症性性传播感染细菌引起的 BALB/c 小鼠炎症的能力证明了包封的白细胞介素-10 的功能。

讨论

总的来说,我们的结果表明成功地对白细胞介素-10 进行了包封,缓慢释放以延长其生物学半衰期,并减少了体外和小鼠体内的炎症细胞因子 IL-6 和 TNF 的产生。我们的结果为进一步探索包封白细胞介素-10 用于生物医学应用(包括炎症性疾病)的治疗前景提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e66/10860865/457c6926f646/IJN-19-1287-g0001.jpg

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